24Mosaic plasmids, plasmids composed of genetic elements from distinct 25 sources, are associated with the spread of antibiotic resistance genes. Transposons 26 are considered the primary mechanism for mosaic plasmid formation, though other 27 mechanisms have been observed in specific instances. The frequency with which 28 mosaic plasmids have been described suggests they may play an important role in 29 plasmid population dynamics. Our survey of the confirmed plasmid sequences 30 available from complete and draft genomes in the RefSeq database shows that 46% 31 of them fit a strict definition of mosaic. Mosaic plasmids are also not evenly 32 distributed over the taxa represented in the database. Plasmids from some genera, 33 including Piscirickettsia and Yersinia, are almost all mosaic, while plasmids from 34 other genera, including Borrelia, are rarely mosaic. While some mosaic plasmids 35 share identical regions with hundreds of others, the median mosaic plasmid only 36 shares with 8 other plasmids. 37 When considering only plasmids from finished genomes (51.6% of the total), 38 mosaic plasmids have significantly higher proportions of transposases and 39 antibiotic resistance genes. Conversely, only 56.6% of mosaic fragments (DNA 40 fragments shared between mosaic plasmids) contain a recognizable transposase, 41 and only 1.2% of mosaic fragments are flanked by inverted repeats. Mosaic 42 fragments associated with the IS26 transposase are 3.8-fold more abundant than 43 any other sequence shared between mosaic plasmids in the database, though this is 44 at least partly due to overrepresentation of Enterobacteriaceae plasmids. 45 Mosaic plasmids are a complicated trait of some plasmid populations, only 46 partly explained by transposition. Though antibiotic resistance genes led to the 47 identification of many mosaic plasmids, mosaic plasmids are a broad phenomenon 48 encompassing many more traits than just antibiotic resistance. Further research 49 will be required to determine the influence of ecology, host repair mechanisms, 50 conjugation, and plasmid host range on the formation and influence of mosaic 51 plasmids. 52 53 Author Summary 54 Plasmids are extrachromosomal genetic entities that are found in many 55 prokaryotes. They serve as flexible storage for genes, and individual cells can make 56 substantial changes to their characteristics by acquiring, losing, or modifying a 57 plasmid. In some pathogenic bacteria, such as Escherichia coli, antibiotic resistance 58 genes are known to spread primarily on plasmids. By analyzing a database of 8,59259 plasmid sequences we determined that many of these plasmids have exchanged 60 genes with each other, becoming mosaics of genes from different sources. We next 61 separated these plasmids into groups based on the organism they were isolated 62 from and found that different groups had different fractions of mosaic plasmids. 63 This result was unexpected and suggests that the mechanisms and selective 64 pressures causing mosaic plasmids do not occur evenly over all s...